The long-term goal of the Physiology Core for the Mesenchymal and Neural Regulation of Metabolic Networks COBRE (PC-MN) is to provide high quality tissue, cellular, and in vivo phenotyping services for Maine Medical Center Research Institute COBRE scientists and other internal investigators, and to share resources with outside investigators. The proposed PC-MN is built on the premise that in order to elucidate the fundamental homeostatic mechanisms of metabolism in the mammal, there must be a standing Core to offer phenotyping services as well as intellectual resources to guide investigator- initiated studies. To achieve this goal, the PC-MN will become the investigative `home' for whole body and tissue phenotyping for each proposed project in the COBRE. Four specific aims are proposed: First, the PC-MN will integrate the infrastructure previously developed in the Physiology Core (as part of the Stem Cell COBRE) and then expand services for in vivo phenotyping in the current COBRE projects. We will offer an array of biochemical assays for investigators for comprehensive hematologic, metabolic and skeletal phenotyping. We will perform dynamic metabolic phenotyping (e.g. energy expenditure, food consumption, physical activity) in animal models and expand services. This will include additional metabolic cages housed in a temperature-controlled chamber, with telemetry for core body temperature analysis, augmented by thermal imaging capabilities, and in vivo NMR and DXA. Second, the PC-MN will provide advanced cellular and mitochondrial bioenergetics by measuring oxidative phosphorylation and glycolysis in cells, selective tissues (e.g. 3D adipose cell cultures in vitro, visceral and inguinal white adipose tissue, brown adipose tissue, neonatal metatarsals, and calvariae) and mitochondria. Third, the PC-MN will counsel investigators in defining the optimal experimental design and then analyzing metabolic profiling of mutant strains, total and fractional tissue mass, energy expenditure, biochemical markers and substrate utilization. Fourth, the PC-MN will maintain the highest quality control while instituting metrics to assess services on a yearly basis. We will continually define and re-evaluate cost structures including charge-back fees for non-COBRE users to insure that the PC-MN will be able to support further expansion of services with new methodologies from colleagues and collaborating scientists. Successful expansion of Physiology Core services and integration with four projects in this COBRE will benefit individual investigators by providing high quality data sets for their proposed projects and for planning future R01 applications. Insights from these basic and translational studies could ultimately be applied in clinical trials of individuals with osteoporosis and obesity.!